AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder

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This study is a Phase 2a, open-label, dose-ranging study of the safety and effectiveness of AA4500 for the treatment of adhesive capsulitis of the shoulder. To be eligible for treatment, a subject must have unilateral idiopathic adhesive capsulitis of the shoulder with restricted range of motion in the affected shoulder for at least 3 months but not more than 12 months. Subjects will be screened for study eligibility within 30 days before injection of study drug.

Approximately 50 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, Assignment to Cohorts 1-4 is sequential. Subjects assigned to Cohorts 1 through 4 may receive up to 3 injections of AA4500 according to cohort assignment. Each injection will be separated by a minimum of 21 days. Subjects assigned to Cohort 5 will receive home shoulder exercises only, while subjects assigned to Cohorts 1-4 will receive AA4500 and home shoulder exercises. Subjects in Cohort 5 will be offered physical therapy sessions for a period of 2 months following completion of the study.

Change From Baseline to Day 92 in Active Forward Flexion [ Time Frame: Baseline, Day 92 ]

Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder

Secondary Outcome Measures :

Change From Baseline to Day 92 in Passive Forward Flexion [ Time Frame: Baseline, Day 92 ]

Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder

Change From Baseline to Day 92 in Active Abduction [ Time Frame: Baseline, Day 92 ]

AROM measurement using a goniometer to assess abduction in the affected shoulder

Change From Baseline to Day 92 in Passive Abduction [ Time Frame: Baseline, Day 92 ]

PROM measurement using a goniometer to assess abduction in the affected shoulder

Change From Baseline to Day 92 in Active External Rotation [ Time Frame: Baseline, Day 92 ]

AROM measurement using a goniometer to assess external rotation in the affected shoulder

Change From Baseline to Day 92 in Passive External Rotation [ Time Frame: Baseline, Day 92 ]

PROM measurement using a goniometer to assess external rotation in the affected shoulder

Change From Baseline to Day 92 in Active Internal Rotation [ Time Frame: Baseline, Day 92 ]

AROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder

Change From Baseline to Day 92 in Passive Internal Rotation [ Time Frame: Baseline, Day 92 ]

PROM measurement using a goniometer to assess internal rotation with the elbow up to 90° abduction in the affected shoulder

Change From Baseline to Day 92 in American Shoulder and Elbow Surgeons (ASES) Composite Score [ Time Frame: Baseline, Day 92 ]

Composite score ranging from 0-100, with 0 being worst pain and function loss, derived from the sum of the scores from pain subscale (11-point NRS where 0=no pain at all and 10=pain) and function subscale (activity questionnaire where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation

Change From Baseline to Day 92 in ASES Pain Subscale [ Time Frame: Baseline, Day 92 ]

Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant assessment of pain in response to "How bad is the pain in your affected shoulder today?" on an 11-point numerical rating scale (NRS) where 0=no pain at all and 10=pain as bad as it can be and calculated as (10 - NRS score) x 5); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation

Change From Baseline to Day 92 in ASES Function Subscale [ Time Frame: Baseline, Day 92 ]

Function subscale score ranging from 0-50, with 0 being most dysfunctional, derived from participant assessment of ability to do 10 activities with affected shoulder/arm where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult, and calculated as (cumulative total score for the 10 activity items) × (5/3); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation

Investigator Assessment of Improvement With Treatment at Day 92 [ Time Frame: Day 92 ]

Investigator assessment of degree of improvement in severity of the participant's treated shoulder compared with screening rated as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Be a male or female and be greater than or equal to 18 years of age

If a female of childbearing potential, have a negative urine pregnancy test and be using an effective contraception method (ie, abstinence, intrauterine device (IUD), hormonal (estrogen/progestin) contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for one menstrual cycle following end of study, or be surgically sterile

Have unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but not more than 12 months before the screening visit and be in Stage 2 (frozen or adhesive stage), as determined by the investigator

Have normal range of motion in the contralateral shoulder, as determined by the investigator

Have restricted active range of motion (AROM) in the affected shoulder defined as: a deficit of at least 60 degrees in total AROM in the affected shoulder as compared with the total AROM in the contralateral shoulder and a deficit of at least 30 degrees in AROM in at least one of the following planes as compared with the contralateral shoulder:

Forward flexion

Abduction

External rotation with the elbow up to 90 degrees abduction

Internal rotation with the elbow up to 90 degrees abduction

Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The subject must also sign an authorization form to allow disclosure of his protected health information (PHI). The PHI authorization form and informed consent form may be an integrated form or may be separate forms depending on the institution.

Be able to complete and understand the various rating instruments in English.

Exclusion Criteria:

Is a pregnant or lactating female or female intending to become pregnant during the study

Is a male who intends to father a child during the study

Has received treatment for adhesive capsulitis or is planning to receive treatment for adhesive capsulitis at any time during the study including but not limited to:

physical therapy or acupuncture within 2 weeks before the first injection of AA4500